A biomechanical perspective on perineal injuries during childbirth

Background and objective: Childbirth trauma is a major health concern that affects millions of women worldwide. Severe degrees of perineal trauma, designated as obstetric anal sphincter injuries (OASIS), and levator ani muscle (LAM) injuries are associated with long-term morbidity. While significant research has been conducted on LAM avulsions, less attention has been given to perineal trauma and OASIS, which affect up to 90% and 11% of vaginal deliveries, respectively. Despite being widely discussed, childbirth trauma remains unpredictable. This work aims to enhance the modeling of the maternal musculature during childbirth, with a particular focus on understanding the mechanisms underlying the often overlooked perineal injuries. Methods: A geometrical model of the pelvic floor muscles (PFM) and perineum (including the perineal body, ischiocavernosus, bulbospongiosus, superficial and deep transverse perineal muscles) was created. The muscles were characterized by a transversely isotropic visco-hyperelastic constitutive model. Two simulations of vaginal delivery were conducted with the fetus in the vertex presentation and occipito-anterior position, with and without the perineum. Results: The simulation that considered the perineum exhibited higher stresses over an extended area of the PFM, which suggests that including additional structures can impact the obtained results. The maximum stretch of the urogenital hiatus was 2.94 and the maximum stress was 23.86 kPa. The perineal body reached a maximum stretch of 1.95, which was more pronounced near the urogenital hiatus, where perineal tears may occur. The external anal sphincter's transverse diameter decreased by 51% and the maximum principal stresses were observed in the area close to the perineal body, where OASIS can occur. Conclusions: The present study emphasizes the importance of including most structures involved in vaginal delivery in its biomechanical analysis and represents another step further in the understanding of perineal injuries and OASIS. The superior region of the perineal body and its connection to the urogenital hiatus and anal sphincter have been identified as the most critical regions, highly susceptible to injury

Finite element modelling of sound transmission from outer to inner ear

The ear is one of the most complex organs in the human body. Sound is a sequence of pressure waves, which propagates through a compressible media such as air. The pinna concentrates the sound waves into the external auditory meatus. In this canal, the sound is conducted to the tympanic membrane. The tympanic membrane transforms the pressure variations into mechanical displacements, which are then transmitted to the ossicles. The vibration of the stapes footplate creates pressure waves in the fluid inside the cochlea; these pressure waves stimulate the hair cells, generating electrical signals which are sent to the brain through the cochlear nerve, where they are decoded. In this work, a three-dimensional finite element model of the human ear is developed. The model incorporates the tympanic membrane, ossicular bones, part of temporal bone (external auditory meatus and tympanic cavity), middle ear ligaments and tendons, cochlear fluid, skin, ear cartilage, jaw and the air in external auditory meatus and tympanic cavity. Using the finite element method, the magnitude and the phase angle of the umbo and stapes footplate displacement are calculated. Two slightly different models are used: one model takes into consideration the presence of air in the external auditory meatus while the other does not. The middle ear sound transfer function is determined for a stimulus of 60 dB SPL, applied to the outer surface of the air in the external auditory meatus. The obtained results are compared with previously published data in the literature. This study highlights the importance of external auditory meatus in the sound transmission. The pressure gain is calculated for the external auditory meatus.info:eu-repo/semantics/publishedVersio

3D models of pelvic floor muscles developed by manual segmentation to FEM

The female pelvic floor is an understudied region of the body from the biomechanical perspective. MRI has been used in the diagnostic evaluation of the pelvic floor dysfunctions. Static images show their morphology while dynamic images show the functional changes that occur on straining and contraction of the pelvic floor. In the present work, MR images contribute to generate 3D solids of pelvic floor muscles through manual segmentation. To study the biomechanical behavior of pelvic floor muscles the Finite Element Method (FEM) would be applied to these 3D solids, contributing to analyze this complex musculature structure. The purpose of this study was to reconstruct tridimensional pelvic floor muscle by manual segmentation and apply FEM. The manual segmentation was made within commercial software. MR images were acquired from the subject supine position, using a 3.0 T system. Field view of the exam was 25×25 cm, 2 mm thick with no gap. The images were acquired in DICOM format, and later converted jpeg format. Twenty consecutive images obtained in the axial plane for each woman were used to construct a 3D model from each of the 8 women. From this 3D reconstruction made through splines in each image, changes in the pubovisceral muscle (a part from the pelvic floor muscles) from the pubis to coccyx were edited. All the pubovisceral muscles edited were exported in step format to the FE analyses software ABAQUS. Finite element meshes were generated for each woman pubovisceral muscle. According to literature soft tissues properties, FE analyses were established to better understand pelvic floor muscles biomechanics. Manual segmentation of the pelvic floor muscles tissues generated very realistic completely different volumetric solids for each woman. It is a very sluggish technique and the nonlinear shape of the pelvic floor makes difficult the utilization of other automatic segmentation

Formalin-fixed and paraffin-embedded samples for next generation sequencing: Problems and solutions

Over the years, increasing information has been asked of the pathologist: we have moved from a purely morphological diagnosis to biomolecular and genetic studies, which have made it possible to implement the use of molecular targeted therapies, such as anti-epidermal growth factor receptor (EGFR) molecules in EGFR-mutated lung cancer, for example. Today, next generation sequencing (NGS) has changed the approach to neoplasms, to the extent that, in a short time, it has gained a place of absolute importance and diagnostic, prognostic and therapeutic utility. In this scenario, formaldehyde-fixed and paraffin-embedded (FFPE) biological tissue samples are a source of clinical and molecular information. However, problems can arise in the genetic material (DNA and RNA) for use in NGS due to fixation, and work is being devoted to possible strategies to reduce its effects. In this paper, we discuss the applications of FFPE tissue samples in the execution of NGS, we focus on the problems arising with the use of this type of material for nucleic acid extraction and, finally, we consider the most useful strategies to prevent and reduce single nucleotide polymorphisms (SNV) and other fixation artifacts

Geometric analysis of female pelvic floor muscles by using manual segmentation

Magnetic Resonance Imaging (MRI) has been used in the diagnostic evaluation of the pelvic floor dysfunctions. MRI can contribute to generate 3D solids of pelvic floor muscles through manual segmentation. The aim of this study is to calculate the area and its moment of inertia of 8 female pelvic floor muscles by using manual segmentation technique. Based on CAD software manual segmentation was used. To build 3D reconstruction models, through of twenty consecutive images. The models were made through splines in each sketch, documenting changes in the pubovisceral muscle (a part from the pelvic floor muscles) from the pubis to coccyx. Two sketches were chosen and biomechanics properties like area and stiffness (moment of inertia) were acquired for each sketch used to generate the pubovisceral muscles. The moment of inertia of the pubovisceral muscle decreases following the order: anterior sketch and posterior sketch. Higher values for the moment of inertia can be encountered in anterior sketcher. This conclusion can lead to more stability in the anterior compartment of pelvic floor visceral

Essential data variables for a minimum dataset for head and neck cancer trials and clinical research:HNCIG consensus recommendations and database

The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research